Study of Safety and Dosing Effect on SMN Levels of Valproic Acid (VPA) in Patients With Spinal Muscular Atrophy

This study has been completed.
Families of Spinal Muscular Atrophy
Sigma Tau Pharmaceuticals, Inc.
Information provided by:
University of Utah Identifier:
First received: September 6, 2006
Last updated: September 11, 2006
Last verified: September 2006
This is an open label phase I/II clinical trial to assess safety, tolerability and potential effect on SMN mRNA and protein in vivo of a compound in which preliminary evidence supports a potential effect on SMN levels in vitro.

Condition Intervention Phase
Spinal Muscular Atrophy
Drug: Valproic Acid
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: In Vivo Study of Safety, Tolerability and Dosing Effect on SMN mRNA and Protein Levels of Valproic Acid in Patients With Spinal Muscular Atrophy

Resource links provided by NLM:

Further study details as provided by University of Utah:

Primary Outcome Measures:
  • To assess safety and tolerability of VPA in SMA patients greater than 2 years of age

Secondary Outcome Measures:
  • To look for a potential in vivo effect of VPA on SMN mRNA in patient blood cells at routinely used clinical doses
  • Measures of gross motor function
  • Electrophysiologic measures of denervation
  • DEXA estimates of body composition, bone mineral density and content
  • Measures of pulmonary function

Estimated Enrollment: 42
Study Start Date: September 2003
Estimated Study Completion Date: February 2006
Detailed Description:
This is an open label phase I/II trial of valproic acid in 40 SMA subjects > 2 years of age with severe, intermediate, and mild phenotypes. Primary outcome measures includes laboratory and physical examination assessments to monitor effects on liver, hematologic, metabolic and nutritional status. Secondary outcomes includes measures of gross motor function; electrophysiologic measures of denervation; DEXA estimates of body composition, bone mineral density and content; measures of pulmonary function; and quantitative SMN mRNA and protein levels in blood cells. Subjects will need 2-3 baseline visits over a 3 -6 month period prior to enrollment. Follow-up visits will be scheduled at 3, 6 and 12 months on treatment.

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have a diagnosis of SMA, confirmed by genetic testing
  • Only patients 2 years of age and older at enrollment will be eligible

Exclusion Criteria:

  • Patients taking any medications with known hepatotoxicity, congenital metabolic disorders or on multiple anticonvulsant medications
  • Patients taking medications which may interact with VPA
  • Patients on ventilatory support for more than 16 hours per day
  • Patients currently enrolled in other treatment trials
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00374075

United States, Utah
University of Utah/Primary Children's Medical Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Utah
Families of Spinal Muscular Atrophy
Sigma Tau Pharmaceuticals, Inc.
Principal Investigator: Kathryn J Swoboda, M.D University of Utah/Primary Children's Medical Center
  More Information

Lindstedt S, Lindstedt G. Distribution and Excretion of Carnitine in the Rat. Acta. Chem. Scand. 1961; 15:701-702
Scriver C, Beautet A, Sly W ,Valle D. The Metabolic Basis of Inherited Disease. New York: McGraw Hill,1989
Schaub J, Van Hoof F, Vis H.Inborn Errors of Metabolism. New York:Raven Press, 1991 Identifier: NCT00374075     History of Changes
Other Study ID Numbers: 11893 
Study First Received: September 6, 2006
Last Updated: September 11, 2006
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
Spinal Muscular Atrophy (SMA)
Valproic Acid

Additional relevant MeSH terms:
Muscular Atrophy
Muscular Atrophy, Spinal
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Nervous System Diseases
Neurodegenerative Diseases
Neurologic Manifestations
Neuromuscular Diseases
Neuromuscular Manifestations
Pathological Conditions, Anatomical
Signs and Symptoms
Valproic Acid
Antimanic Agents
Central Nervous System Depressants
Enzyme Inhibitors
GABA Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Psychotropic Drugs
Tranquilizing Agents processed this record on May 24, 2016